Neural and Behavioral Effects of a Novel Mu Opioid Receptor Antagonist in Binge-Eating Obese People
Neural and Behavioral Effects of a Novel Mu Opioid Receptor Antagonist in Binge-Eating Obese People
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DOI：
10.1016/j.biopsych.2012.10.022
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发表时间：
2013-05-01
影响因子：
10.6
通讯作者：
Fletcher, Paul C.
中科院分区：
文献类型：
--
作者：
Cambridge, Victoria C.;Ziauddeen, Hisham;Fletcher, Paul C.
背景：暴饮暴食与肥胖有关，已被概念化为“食物成瘾”。然而，这一观点在人类中只得到了不一致的支持，而且有限的证据表明关键的神经回路与这种疾病有关。此外，使用药理功能磁共振成像来探索进食行为改变的潜在基础的研究相对较少。方法：在一项双盲、安慰剂对照、平行分组研究中，我们探索了一种有效的阿片受体拮抗剂GSK1521498在中度暴饮暴食的肥胖者中的作用。受试者在基线安慰剂磨合期进行测试，并在药物(n=21)或安慰剂(n=21)治疗28天后重新测试。通过功能磁共振成像和行为测量，我们分别确定了药物对大脑对食物图像的反应以及对花费能量观看可比图像的动机的影响。结果：与安慰剂相比，GSK1521498显著降低了对高热量食物图像的苍白球/壳核反应，并降低了观看高热量食物图像的动机。有趣的是，尽管动机反应降低了，但在药物治疗后，对相同图像的主观喜好实际上增加了。结论：暴饮暴食的肥胖者的刺激特异性壳核/苍白球反应对改变的mu阿片类药物功能敏感。这种神经调节伴随着动机反应的减少，这是通过握力来衡量的，尽管对相同刺激的主观喜好反应实际上增加了。这些结果不仅为暴饮暴食的肥胖者的阿片系统和食物相关行为之间的联系提供了证据，还支持了这些人与食物相关刺激相关的动机和喜好的衡量标准之间的分离。
Background: Binge eating is associated with obesity and has been conceptualized as "food addiction." However, this view has received only inconsistent support in humans, and limited evidence relates key neurocircuitry to the disorder. Moreover, relatively few studies have used pharmacologic functional magnetic resonance imaging to probe the underlying basis of altered eating behaviors.Methods: In a double-blind, placebo-controlled, parallel group study, we explored the effects of a potent mu-opioid receptor antagonist, GSK1521498, in obese individuals with moderate binge eating. Subjects were tested during a baseline placebo run-in period and retested after 28-days of drug (n = 21) or placebo (n = 21) treatment. Using functional magnetic resonance imaging and behavioral measures, we determined the drug's effects on brain responses to food images and, separately, on motivation to expend energy to view comparable images.Results: Compared with placebo, GSK1521498 was associated with a significant reduction in pallidum/putamen responses to pictures of high-calorie food and a reduction in motivation to view images of high-calorie food. Intriguingly, although motivational responding was reduced, subjective liking for the same images actually increased following drug treatment.Conclusions: Stimulus-specific putamen/pallidal responses in obese people with binge eating are sensitive to altered mu-opioid function. This neuromodulation was accompanied by reductions in motivational responding, as measured by grip force, although subjective liking responses to the same stimuli actually increased. As well as providing evidence for a link between the opioid system and food-related behavior in binge-eating obese individuals, these results support a dissociation across measures of motivation and liking associated with food-related stimuli in these individuals.